The prevalence of substance use is disproportionately high among Hispanic youth in the U.S., and substance use is increasing in Latin America. Yet substance use in Hispanic populations is vastly understudied. The relatively few studies with Hispanics consist mainly of cross-sectional samples or very short longitudinal designs (e.g., 2-3 years). They tend to rely on samples of school-attending youth and do not include information on biological insults that might impact later substance use. The proposed project addresses many of these limitations. It builds on an extraordinary sample of over 1,200 young Chilean adolescents and their families, who have been followed longitudinally since infancy. The sample was originally enrolled in conjunction with a NIH-supported study of the behavioral and developmental effects of preventing iron deficiency anemia in infancy. Comprehensive information on biological, individual, familial, and environmental factors was obtained in infancy and at 5 and 10 years. The children will be 11-15 years at the start of the proposed project, an age period when initiation of substance use, especially alcohol and tobacco, is exceptionally high in Chile. We propose to identify developmental pathways of substance use, abuse, and dependence in early to late adolescence. In the proposed five-year study we plan to conduct two comprehensive assessments of all adolescent-mother dyads, approximately two years apart. Guided by a life-course approach, we propose to investigate 3 Specific Aims: Aim 1) To longitudinally characterize individual, familial, and environmental factors from infancy through adolescence that increase or decrease drug involvement in adolescence;Aim 2) To identify cognitive, behavioral, and social consequences of substance use through an at-risk period and beyond;and Aim 3) To determine the effects of a probable insult to the dopamine system in infancy (iron deficiency) on substance use and abuse in adolescence. Findings from the proposed study can contribute to our understanding of the etiology and prevention of substance use and abuse in two important ways: 1) To further the identification of pathways of drug involvement among Hispanic youth;and 2) To study developmental pathways of substance use within a multiple domain context that ranges from the biological to the environmental over a 15-year period.